“Complement”ary MRSA fight

Thymic stromal lymphopoietin (TSLP) is a cytokine thought to promote allergic responses; however, its role in fighting infectious diseases is less clear. Now, West et al. report that TSLP in the skin can enhance killing of methicillin-resistant Staphylococcus aureus (MRSA). TSLP enhances killing in both mouse and human neutrophils, in part through interactions with the complement system that induce reactive oxygen species in neutrophils. This enhanced killing is not limited to MRSA because TSLP also boosts killing of Streptococcus pyogenes. These data suggest that TSLP may augment innate immune cells and complement to fight bacterial infection.

Abstract

Community-acquired Staphylococcus aureus infections often present as serious skin infections in otherwise healthy individuals and have become a worldwide epidemic problem fueled by the emergence of strains with antibiotic resistance, such as methicillin-resistant S. aureus (MRSA). The cytokine thymic stromal lymphopoietin (TSLP) is highly expressed in the skin and in other barrier surfaces and plays a deleterious role by promoting T helper cell type 2 (TH2) responses during allergic diseases; however, its role in host defense against bacterial infections has not been well elucidated. We describe a previously unrecognized non-TH2 role for TSLP in enhancing neutrophil killing of MRSA during an in vivo skin infection. Specifically, we demonstrate that TSLP acts directly on both mouse and human neutrophils to augment control of MRSA. Additionally, we show that TSLP also enhances killing of Streptococcus pyogenes, another clinically important cause of human skin infections. Unexpectedly, TSLP mechanistically mediates its antibacterial effect by directly engaging the complement C5 system to modulate production of reactive oxygen species by neutrophils. Thus, TSLP increases MRSA killing in a neutrophil- and complement-dependent manner, revealing a key connection between TSLP and the innate complement system, with potentially important therapeutic implications for control of MRSA infection.